GFI1 and GFI1B control the loss of endothelial identity of hemogenic endothelium during hematopoietic commitment
GFI1 and GFI1B control the loss of endothelial identity of hemogenic endothelium during hematopoietic commitment
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DOI：
10.1182/blood-2011-10-386094
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发表时间：
2012-07-12
期刊：
影响因子：
20.3
通讯作者：
Lacaud, Georges
中科院分区：
文献类型：
--
作者：
Lancrin, Christophe;Mazan, Milena;Lacaud, Georges
最近的研究已经确定，在胚胎发育期间，造血祖细胞和干细胞通过称为内皮向造血转变（EHT）的过程从生血内皮前体产生。转录因子RUNX 1在这一过程中是必不可少的，但其主要的下游效应子仍在很大程度上未知。在这里，我们报告了Gfi 1和Gfi 1b作为RUNX 1的直接靶点和EHT的关键调节剂的鉴定。GFI 1和GFI 1B能够在RUNX 1不存在的情况下触发内皮标志物的下调和圆形细胞的形成，这是EHT的特征性形态学变化。相反，Gfi 1和Gfi 1b缺陷胚胎中的血液祖细胞维持内皮基因的表达。此外，这些细胞不会从卵黄囊释放并散布到胚胎组织中。综上所述，我们的研究结果表明，GFI 1转录因子的关键和特定的作用，在第一步的过程中，导致造血祖细胞的生成从生血内皮细胞。（血。2012; 120（2）：314-322）
Recent studies have established that during embryonic development, hematopoietic progenitors and stem cells are generated from hemogenic endothelium precursors through a process termed endothelial to hematopoietic transition (EHT). The transcription factor RUNX1 is essential for this process, but its main downstream effectors remain largely unknown. Here, we report the identification of Gfi1 and Gfi1b as direct targets of RUNX1 and critical regulators of EHT. GFI1 and GFI1B are able to trigger, in the absence of RUNX1, the down-regulation of endothelial markers and the formation of round cells, a morphologic change characteristic of EHT. Conversely, blood progenitors in Gfi1- and Gfi1b-deficient embryos maintain the expression of endothelial genes. Moreover, those cells are not released from the yolk sac and disseminated into embryonic tissues. Taken together, our findings demonstrate a critical and specific role of the GFI1 transcription factors in the first steps of the process leading to the generation of hematopoietic progenitors from hemogenic endothelium. (Blood. 2012; 120(2): 314-322)